Experiments in progress and planned are designed to elucidate the molecular basis of bio-electrical phenomena in excitable cells. Involved in our studies are the enzyme acetylcholinesterase, the associated acetylcholine receptor, and the ion fluxes across excitable membranes, which are initiated and controlled by the interactions of specific ligands and the receptor. Single cells and membrane preparations from the electric organ of Electrophorus electricus, Torpedo ocellata, and cells in culture, are used. The regulatory process observed in this relatively defined system is considered to be identical to that at a nerve synapse. It is hoped to obtain information about the mechanism of interaction of ligands with the receptor using equilibrium and kinetic measurements, about the topography of the ligand-binding sites of the receptor using specific fluorescent labels, about molecular changes in the receptor which correlate with ion flux, and about the detailed balance of ions on both sides of the membrane. Previously, quantitative investigations of the physiological effect of interactions between chemical mediators and the receptor have been restricted to measurements on single electroplax cells. Techniques have been developed to allow quantitative studies with membrane vesicles. A variety of techniques including flow and relaxation methods are being used. BIBLIOGRAPHIC REFERENCES: Fu, J.-j.L., Donner, D.B., Moore, D.E., and Hess, G.P. Biochemistry 16, 678-683 (1977) Allosteric interactions between the membrane-bound acetylcholine receptor and chemical mediators: Equilibrium measurements. Bulger, J.E., Fu, J.-j.L., Hindy, E.F., Silberstein, R.L., and Hess, G.P. Biochemistry 16, 684-692 (1977) Allosteric interactions between the membrane-bound acetylcholine receptor and chemical mediators. Kinetic studies.